Numerous investigators have shown that declining immunologic vigor is a regular concomitant of aging. We discovered that this aspect of aging is more prominent in certain strains of mice than others and that it is accompanied by increasing autoimmunity. These changes are accelerated by thymectomy. In mice where immunologic deficiency and autoimmunity are observed during aging, preliminary evidence indicates associated thymic involution, loss of thymic dependent cells and decreased cellular- mediated immune functions. The objectives of our investigations are: to analyze the basis for declining immunologic vigor and increasing incidence of autoimmunity with aging and to test the relative capacities of thymus stroma, stem cells, and immunocompetent cells of young and aging autoimmune susceptible and resistant strains to restore immune functions and prolong life in neonatally thymectomized and aging mice. Experimental models will include: 1) thymectomized mice lacking site for differentiation of stem cells but possessing post-thymic cells, 2) thymectomized irradiated mice which lack post-thymic cells; 3) supralethally irradiated mice to test aging effects on stem cells and 4) aged mice for analysis of thymus peripheral lymphoid cells, thymus humoral influence, stem cells and their combination on the waning immune vigor. Thus the meaning of involution of the thymus and its system with respect to development of immune deficiency and autoimmunity with aging can be effectively assessed at the cellular level. Understanding of these relationships should ultimately help prolong useful life in man.